Nephropathy in Pparg-null mice highlights PPARγ systemic activities in metabolism and in the immune system.

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor involved in many aspects of metabolism, immune response, and development. Total-body deletion of the two Pparg alleles provoked generalized lipoatrophy along with severe type 2 diabetes. Herein, we explore the appearance and development of structural and functional alterations of the kidney, comparing Pparg null-mice to their littermate controls (carrying Pparg floxed alleles). We show that renal hypertrophy and functional alterations with increased glucosuria and albuminuria are already present in 3 weeks-old Pparg null-mice. Renal insufficiency with decreased creatinine clearance progress at 7 weeks of age, with the advance of the type 2 diabetes. At 52 weeks of age, these alterations are accompanied by signs of fibrosis and mesangial expansion. More intriguingly, aged Pparg null-mice concomitantly present an anti-phospholipid syndrome (APS), characterized by the late appearance of microthrombi and a mesangioproliferative pattern of glomerular injury, associated with significant plasmatic levels of anti-β2- glycoprotein1 antibodies and renal deposition of IgG, IgM, and C3. Thus, in line with the role of PPARγ in metabolic homeostasis, Pparg null-mice first represent a potent model for studying the initiation and the development of diabetic nephropathy. Second, and in relation with the important PPARγ activity in inflammation and in immune system, these mice also highlight a new role for PPARγ signaling in the promotion of APS, a syndrome whose pathogenesis is poorly known and whose current treatment is limited to prevention of thrombosis events

SN 2010ay is a Luminous and Broad-lined Type Ic Supernova within a Low-metallicity Host Galaxy

We report on our serendipitous pre-discovery detection and detailed follow-up of the broad-lined Type Ic supernova (SN) 2010ay at z = 0.067 imaged by the Pan-STARRS1 3pi survey just ~4 days after explosion. The SN had a peak luminosity, M_R ~ -20.2 mag, significantly more luminous than known GRB-SNe and one of the most luminous SNe Ib/c ever discovered. The absorption velocity of SN 2010ay is v_Si ~ 19,000 km/s at ~40 days after explosion, 2-5 times higher than other broad-lined SNe and similar to the GRB-SN 2010bh at comparable epochs. Moreover, the velocity declines ~2 times slower than other SNe Ic-BL and GRB-SNe. Assuming that the optical emission is powered by radioactive decay, the peak magnitude implies the synthesis of an unusually large mass of 56 Ni, M_Ni = 0.9 M_solar. Modeling of the light-curve points to a total ejecta mass, M_ej ~ 4.7 M_sol, and total kinetic energy, E_K ~ 11x10^51 ergs. The ratio of M_Ni to M_ej is ~2 times as large for SN 2010ay as typical GRB-SNe and may suggest an additional energy reservoir. The metallicity (log(O/H)_PP04 + 12 = 8.19) of the explosion site within the host galaxy places SN 2010ay in the low-metallicity regime populated by GRB-SNe, and ~0.5(0.2) dex lower than that typically measured for the host environments of normal (broad-lined) Ic supernovae. We constrain any gamma-ray emission with E_gamma < 6x10^{48} erg (25-150 keV) and our deep radio follow-up observations with the Expanded Very Large Array rule out relativistic ejecta with energy, E > 10^48 erg. We therefore rule out the association of a relativistic outflow like those which accompanied SN 1998bw and traditional long-duration GRBs, but place less-stringent constraints on a weak afterglow like that seen from XRF 060218. These observations challenge the importance of progenitor metallicity for the production of a GRB, and suggest that other parameters also play a key role.Comment: 19 pages, 10 figures, V3 has revisions following referee's report; more information at http://www.cfa.harvard.edu/~nsanders/papers/2010ay/summary.htm

The Optical SN 2012bz Associated with the Long GRB 120422A

The association of Type Ic SNe with long-duration GRBs is well established. We endeavor, through accurate ground-based observational campaigns, to characterize these SNe at increasingly high redshifts. We obtained a series of optical photometric and spectroscopic observations of the Type Ic SN2012bz associated with the Swift long-duration GRB120422A (z=0.283) using the 3.6-m TNG and the 8.2-m VLT telescopes. The peak times of the light curves of SN2012bz in various optical filters differ, with the B-band and i'-band light curves reaching maximum at ~9 and ~23 rest-frame days, respectively. The bolometric light curve has been derived from individual bands photometric measurements, but no correction for the unknown contribution in the near-infrared (probably around 10-15%) has been applied. Therefore, the present light curve should be considered as a lower limit to the actual UV-optical-IR bolometric light curve. This pseudo-bolometric curve reaches its maximum (Mbol = -18.56 +/- 0.06) at 13 +/- 1 rest-frame days; it is similar in shape and luminosity to the bolometric light curves of the SNe associated with z<0.2 GRBs and more luminous than those of SNe associated with XRFs. A comparison with the model generated for the bolometric light curve of SN2003dh suggests that SN2012bz produced only about 15% less 56Ni than SN2003dh, about 0.35 Msol. Similarly the VLT spectra of SN2012bz, after correction for Galactic extinction and for the contribution of the host galaxy, suggest comparable explosion parameters with those observed in SN2003dh (EK~3.5 x 10^52 erg, Mej~7 Msol) and a similar progenitor mass (~25-40 Msol). GRB120422A is consistent with the Epeak-Eiso and the EX,iso-Egamma,iso-E_peak relations. GRB120422A/SN2012bz shows the GRB-SN connection at the highest redshift so far accurately monitored both photometrically and spectroscopically.Comment: 7 pages, 6 figures, 2 tables, accepted for publication in Astronomy & Astrophysic

X-Ray Observations of Type Ia Supernovae with Swift: Evidence for Circumstellar Interaction for SN 2005ke

We present a study of the early (days to weeks) X-ray and UV properties of eight Type Ia supernovae (SNe Ia) which have been extensively observed with the X-Ray Telescope (XRT) and UV/Optical Telescope (UVOT) onboard Swift, ranging from 5-132 days after the outburst. SN 2005ke is tentatively detected (at a 3-3.6 sigma level of significance) in X-rays based on deep monitoring with the XRT ranging from 8 to 120 days after the outburst. The inferred X-ray luminosity [(2+/-1) x 10^{38} ergs/s; 0.3-2 keV band] is likely caused by interaction of the SN shock with circumstellar material (CSM), deposited by a stellar wind from the progenitor's companion star with a mass-loss rate of ~ 3 x 10^{-6} M_sun/yr (v_w/10 km/s). Evidence of CSM interaction in X-rays is independently confirmed by an excess of UV emission as observed with the UVOT onboard Swift, starting around 35 days after the explosion. The non-detection of SN 2005ke with Chandra 105 days after the outburst implies a rate of decline steeper than L_x \propto t^{-0.75}, consistent with the decline expected from the interaction of the SN shock with a spherically symmetric CSM (t^{-1}). None of the other seven SNe Ia is detected in X-rays or shows a UV excess, which allows us to put tight constraints on the mass-loss rates of the progenitor systems.Comment: 12 pages, 3 figures, accpeted for publication in ApJ

The Broad-lined Type Ic SN 2003jd

The results of a world-wide coordinated observational campaign on the broad-lined Type Ic SN 2003jd are presented. In total, 74 photometric data points and 26 spectra were collected using 11 different telescopes. SN 2003jd is one of the most luminous SN Ic ever observed. A comparison with other Type Ic supernovae (SNe Ic) confirms that SN 2003jd represents an intermediate case between broad-line events (2002ap, 2006aj), and highly energetic SNe (1997ef, 1998bw, 2003dh, 2003lw), with an ejected mass of M_{ej} = 3.0 +/- 1 Mo and a kinetic energy of E_{k}(tot) = 7_{-2}^{+3} 10^{51} erg. SN 2003jd is similar to SN 1998bw in terms of overall luminosity, but it is closer to SNe 2006aj and 2002ap in terms of light-curve shape and spectral evolution. The comparison with other SNe Ic, suggests that the V-band light curves of SNe Ic can be partially homogenized by introducing a time stretch factor. Finally, due to the similarity of SN 2003jd to the SN 2006aj/XRF 060218 event, we discuss the possible connection of SN 2003jd with a GRB.Comment: 19 pages, 19 figures, Accepted for publication in MNRA

Diabetes and heart failure associations in women and men: results from the MORGAM consortium

Background: Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe. Methods: This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome. Results: 6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58–1.89] and 2.12 [1.91–2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75–16.41] for women with T1DM vs. 5.80 [2.72–12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93–2.54] vs. 1.99 [1.67–2.38] respectively, p for interaction 0.80). Conclusion: Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex

Chandra Observations of Type Ia Supernovae: Upper Limits to the X-ray Flux of SN 2002bo, SN 2002ic, SN 2005gj, and SN 2005ke

We set sensitive upper limits to the X-ray emission of four Type Ia supernovae (SNe Ia) using the Chandra X-ray Observatory. SN 2002bo, a normal, although reddened, nearby SN Ia, was observed 9.3 days after explosion. For an absorbed, high temperature bremsstrahlung model the flux limits are 3.2E-16 ergs/cm^2/s (0.5-2 keV band) and 4.1E-15 ergs/cm^2/s (2-10 keV band). Using conservative model assumptions and a 10 km/s wind speed, we derive a mass loss rate of \dot{M} ~ 2E-5 M_\odot/yr, which is comparable to limits set by the non-detection of Halpha lines from other SNe Ia. Two other objects, SN 2002ic and SN 2005gj, observed 260 and 80 days after explosion, respectively, are the only SNe Ia showing evidence for circumstellar interaction. The SN 2002ic X-ray flux upper limits are ~4 times below predictions of the interaction model currently favored to explain the bright optical emission. To resolve this discrepancy we invoke the mixing of cool dense ejecta fragments into the forward shock region, which produces increased X-ray absorption. A modest amount of mixing allows us to accommodate the Chandra upper limit. SN 2005gj is less well studied at this time. Assuming the same circumstellar environment as for SN 2002i, the X-ray flux upper limits for SN 2005gj are ~4 times below the predictions, suggesting that mixing of cool ejecta into the forward shock has also occurred here. Our reanalysis of Swift and Chandra data on SN 2005ke does not confirm a previously reported X-ray detection. The host galaxies NGC 3190 (SN 2002bo) and NGC 1371 (SN 2005ke) each harbor a low luminosity (L_X ~ 3-4E40 ergs/s) active nucleus in addition to wide-spread diffuse soft X-ray emission.Comment: 16 pages, to appear in ApJ (20 Nov 2007

PS1-10afx at z=1.388: Pan-STARRS1 Discovery of a New Type of Superluminous Supernova

We present the Pan-STARRS1 discovery of PS1-10afx, a unique hydrogen-deficient superluminous supernova (SLSN) at z=1.388. The light curve peaked at z_P1=21.7 mag, making PS1-10afx comparable to the most luminous known SNe, with M_u = -22.3 mag. Our extensive optical and NIR observations indicate that the bolometric light curve of PS1-10afx rose on the unusually fast timescale of ~12 d to the extraordinary peak luminosity of 4.1e44 erg/s (M_bol = -22.8 mag) and subsequently faded rapidly. Equally important, the SED is unusually red for a SLSN, with a color temperature of 6800 K near maximum light, in contrast to previous H-poor SLSNe, which are bright in the UV. The spectra more closely resemble those of a normal SN Ic than any known SLSN, with a photospheric velocity of 11,000 km/s and evidence for line blanketing in the rest-frame UV. Despite the fast rise, these parameters imply a very large emitting radius (>5e15 cm). We demonstrate that no existing theoretical model can satisfactorily explain this combination of properties: (i) a nickel-powered light curve cannot match the combination of high peak luminosity with the fast timescale; (ii) models powered by the spindown energy of a rapidly-rotating magnetar predict significantly hotter and faster ejecta; and (iii) models invoking shock breakout through a dense circumstellar medium cannot explain the observed spectra or color evolution. The host galaxy is well detected in pre-explosion imaging with a luminosity near L*, a star formation rate of 15 M_sun/yr, and is fairly massive (2e10 M_sun), with a stellar population age of 1e8 yr, also in contrast to the dwarf hosts of known H-poor SLSNe. PS1-10afx is distinct from known examples of SLSNe in its spectra, colors, light-curve shape, and host galaxy properties, suggesting that it resulted from a different channel than other hydrogen-poor SLSNe.Comment: 17 pages, 12 figures, accepted to ApJ, minor revisions, including expanded discussion of lensing hypothesi

An optical supernova associated with the X-ray flash XRF 060218

Long-duration gamma-ray bursts (GRBs) are associated with type Ic supernovae that are more luminous than average and that eject material at very high velocities. Less-luminous supernovae were not hitherto known to be associated with GRBs, and therefore GRB-supernovae were thought to be rare events. Whether X-ray flashes - analogues of GRBs, but with lower luminosities and fewer gamma-rays - can also be associated with supernovae, and whether they are intrinsically 'weak' events or typical GRBs viewed off the axis of the burst, is unclear. Here we report the optical discovery and follow-up observations of the type Ic supernova SN 2006aj associated with X-ray flash XRF 060218. Supernova 2006aj is intrinsically less luminous than the GRB-supernovae, but more luminous than many supernovae not accompanied by a GRB. The ejecta velocities derived from our spectra are intermediate between these two groups, which is consistent with the weakness of both the GRB output and the supernova radio flux. Our data, combined with radio and X-ray observations, suggest that XRF 060218 is an intrinsically weak and soft event, rather than a classical GRB observed off-axis. This extends the GRB-supernova connection to X-ray flashes and fainter supernovae, implying a common origin. Events such as XRF 060218 are probably more numerous than GRB-supernovae.Comment: Final published versio

Zooming In on the Progenitors of Superluminous Supernovae With the HST

We present Hubble Space Telescope (HST) rest-frame ultraviolet imaging of the host galaxies of 16 hydrogen-poor superluminous supernovae (SLSNe), including 11 events from the Pan-STARRS Medium Deep Survey. Taking advantage of the superb angular resolution of HST, we characterize the galaxies' morphological properties, sizes and star formation rate (SFR) densities. We determine the supernova (SN) locations within the host galaxies through precise astrometric matching, and measure physical and host-normalized offsets, as well as the SN positions within the cumulative distribution of UV light pixel brightness. We find that the host galaxies of H-poor SLSNe are irregular, compact dwarf galaxies, with a median half-light radius of just 0.9 kpc. The UV-derived SFR densities are high ( ~ 0.1 M_sun/yr/kpc^2), suggesting that SLSNe form in overdense environments. Their locations trace the UV light of their host galaxies, with a distribution intermediate between that of long-duration gamma-ray bursts (LGRBs) (which are strongly clustered on the brightest regions of their hosts) and a uniform distribution (characteristic of normal core-collapse SNe), though cannot be statistically distinguished from either with the current sample size. Taken together, this strengthens the picture that SLSN progenitors require different conditions than those of ordinary core-collapse SNe to form, and that they explode in broadly similar galaxies as do LGRBs. If the tendency for SLSNe to be less clustered on the brightest regions than are LGRBs is confirmed by a larger sample, this would indicate a different, potentially lower-mass progenitor for SLSNe than LRGBs.Comment: ApJ in press; matches published version. Minor changes following referee's comments; conclusions unchange